The η-class carbonic anhydrases as drug targets for antimalarial agents.
The η-class of carbonic anhydrases (CAs, EC 18.104.22.168) was recently discovered as the sixth genetic family of this metalloenzyme superfamily, and seems to be present only in various Plasmodium species, the malaria-provoking pathogens. The present review through detailed biochemical, kinetic and phylogenetic studies afford a clear view regarding the differences between η- and the other CA families. In this review, the authors underlined as the η-CAs, like α-, γ- and δ-class enzymes, have the Zn(II) ion coordinated by three histidine residues and a water molecule. They seem to be more closely related to the α-CAs, but there are notable differences between them, such as the lack of the proton shuttle residue (His64) and gatekeeper residues, Glu106 and Thr199 in the η-CAs, which are conserved in all α-CAs. Plasmodium falciparum η-CA showed a moderate but significant activity for the CO2 hydration reaction, with a kcat of 1.4 × 10(5)s(-1) and a kcat/Km of 5.4 × 10(6) M(-1) × s(-1). Several inhibition studies with anions and sulfonamides/sulfamates, allowed the identification of interesting lead compounds. The discovery of η-CA-specific inhibitors may lead to novel such agents with a new mechanism of action.


[Women and cardiovascular diseases].
The authors draw attention to the important role played by menopause in the onset of arterial hypertension, enhanced coronary risk and dyslipidemia, for which a particularly useful association has been found to be estrogens, only if administered by mouth (alone or with progestins), and statins. The authors review numerous studies for or against the use of estrogens as a means of reducing arterial hypertension and the incidence of myocardial ischemia in menopausal women. In order to ensure therapeutic efficacy, replacement estrogen therapy should not be started at not too late an age, but instead as young as possible (the first 5 years after the start of menopause are optimal), namely before levels of endothelial estrogen receptors start to fall. Moreover, therapy should not be continued for more than 5 years in order to avoid the risk of breast cancer and endometrial carcinoma. With regard to myocardial infarction, it is worth noting that women show a higher frequency of silent and atypical infarction leading to a late diagnosis and therefore the arrival in the coronary unit half an hour or an hour later than men. Together with the onset of myocardial infarction at an older age in women compared to men (5-10 years), and the fact that diagnosis is less accurate in women and treatment less sophisticated, this accounts for the higher immediate and medium-term mortality figures in women following myocardial infarction. However, at least in America studies have shown that the less aggressive diagnostic and therapeutic management of myocardial infarction in women compared to men is not sufficient to cause a significant difference in mortality between men and women 30 days after the event. Turning to arrhythmia, it is worth recalling that supraventricular tachycardia with close rapid complexes, caused by return in the atrioventricular node is more frequent in females and in the second lutein or progestin phase of the menstrual cycle, thus demonstrating the protective role of estrogens against the onset of arrhythmia. The authors also point out the frequent association between ischemic ictus and chronic non-valvular atrial fibrillation in women aged over 75 since they present a very high risk (94%) of death by ischemic ictus. On the one hand, the guidelines recommend the use of anticoagulating therapy in these patients, but on the other there is a very high risk of hemorrhage which acts as a major constraint. Lastly, pregnancy is mentioned as a condition that facilitates the onset of arrhythmia; for example, orthodromic supraventricular tachycardia in Wolf Parkinson White and ventricular tachycardia which usually regresses post-partum.


[Recent knowledge and hypotheses on the significance of the HLA-D region in rheumatoid arthritis].
Rheumatoid arthritis (RA) may result from an interaction between genetic and environmental factors. There is a well documented association between RA and the serologically defined class II MHC antigen haplotype DR4-DRw53-DQw3. Cellular HLA typing reveals five Dw subtypes (Dw4, 10, 13, 14, 15) of this haplotype. DNA coding for this Dw-subtypes occurs in the third hypervariable region (3. HVR) of the DR beta 1 domain suggesting, that this part of the molecule is recognized by T cells. Relatively circumscribed amino acid changes in this 3. HVR, which contains an alpha-helical structure, may result in immune response changes. Susceptibility to RA may be due to related epitopes found in non-Dw10 subtypes of DR4, as well as in DR1 alleles. Studies, using T cell clones specific for the Dw14 subtype of DR4 found Dw14-associated epitopes in 100% (!) also on non-DR4 haplotypes, in the population with RA. Typing with primed lymphocytes may give rise to the association of HLA and RA.


Total flavonoids from Smilax glabra Roxb blocks epithelial-mesenchymal transition and inhibits renal interstitial fibrosis by targeting miR-21/PTEN signaling.
Smilax glabra Roxb, a traditional Chinese herb, has been widely used in folk medicine. The current study was performed to investigate the protective effect of S. glabra Roxb extract, pure total flavonoids from Smilax glabra Roxb (PTFS), on renal interstitial fibrosis (RIF) and its underlying mechanism. First, a surgical model of unilateral ureteral obstruction was established in rats to induce RIF. Then, rats were grouped and treated with PTFS at different concentration. Second, HK-2 cells underwent an epithelial-mesenchymal transition (EMT) by the addition of transforming growth factor-β1 (TGF-β1). Additionally, HK-2 cells after inducing for EMT were transfected with microRNA-21 (miR-21) mimic or inhibitor. These HK-2 cells were grouped and treated with PTFS at different concentration. Finally, real-time polymerase chain reaction and Western blot analysis were performed to detect the expression of possible signaling factor involved in RIF in renal tissues or HK-2 cells after PTFS treatment. In vivo and in vitro experiments indicated that PTFS treatment could decrease the expression of α-smooth muscle actin (α-SMA; mesenchymal marker) and increase the expression of E-cadherin (epithelial marker) in both messenger RNA and protein level. Moreover, PTFS also attenuated the expression of TGF-β1/Smad signaling in both renal tissues and HK-2 cells that underwent EMT. Overexpression or inhibition of miR-21 in HK-2 cells activated or blocked the PI3K/Akt signaling via targeting phosphatase and tension homolog (PTEN), and then promoted or suppressed the progress of TGF-β1-induced EMT by regulating the expression of α-SMA and E-cadherin. Furthermore, PTFS treatment inhibited TGF-β1-induced EMT progress by blocking miR-21/PTEN/PI3K/Akt signaling. PTFS has strong anti-EMT and antifibrosis effects both in vitro and in vivo. The mechanism underlying these effects may be related to inhibition of TGF-β1/Smad, and their downstream miR-21/PTEN signaling, leading to blocks of EMT process during RIF.


Divalent folate modification on PEG: an effective strategy for improving the cellular uptake and targetability of PEGylated polyamidoamine-polyethylenimine copolymer.
The stability and targeting ability of nanocarrier gene delivery systems are necessary conditions to ensure the good therapeutic effect and low nonspecific toxicity of cancer treatment. Poly(ethylene glycol) (PEG) has been widely applied for improving stability and as a spacer for linking ligands and nanocarriers to improve targetability. However, the cellular uptake and endosomal escape capacity of nanocarriers has been seriously harmed due to the introduction of PEG. In the present study, we synthesized a new gene delivery vector by coupling divalent folate-PEG (PEG3.4k-FA2) onto polyamidoamine-polyethylenimine (PME) copolymer (PME-(PEG3.4k-FA2)1.72). Both PEG and monovalent folate-PEG (PEG3.4k-FA1) modified PME were prepared as control polymers, which were named as PME-(PEG3.5k)1.69 and PME-(PEG3.4k-FA1)1.66, respectively. PME-(PEG3.4k-FA2)1.72 exhibited strong DNA condensation capacity like parent polymer PME which was not significantly influenced by PEG. PME-(PEG3.4k-FA2)1.72/DNA complexes at N/P = 10 had a diameter ∼143 nm and zeta potential ∼13 mV and showed the lowest cytotoxicity and hemolysis and the highest transfection efficiency among all tested polymers. In folate receptor positive (FR-positive) cells, the cellular uptake and transfection efficiency were increased with the increase in the number of folates coupled on PEG; the order was PME-(PEG3.4k-FA2)1.72 > PME-(PEG3.4k-FA1)1.66 > PME-(PEG3.5k)1.69. Folate competition assays showed that PME-(PEG3.4k-FA2)1.72 complexes had stronger targeting ability than PME-(PEG3.5k)1.69 and PME-(PEG3.4k-FA1)1.66 complexes due to their higher folate density per PEG molecule. Cellular uptake mechanism study showed that the folate density on PEG could change the endocytosis pathway of PME-(PEG3.5k)1.69 from clathrin-mediated endocytosis to caveolae-mediated endocytosis, leading to less lysosomal degradation. Distribution and uptake in 3D multicellular spheroid assays showed that divalent folate could offer PME-(PEG3.4k-FA2)1.72 complexes stronger penetrating ability and higher cellular uptake. With these advantages, PME-(PEG3.4k-FA2)1.72 may be a promising nonviral vector candidate for efficient gene delivery. This study also indicates that divalent folate modification on PEG can serve as an efficient strategy to improve the cellular uptake and targeting ability of PEGylated cationic polymers for gene delivery.


High-energy photon activation tandem mass spectrometry provides unprecedented insights into the structure of highly sulfated oligosaccharides extracted from macroalgal cell walls.
Extreme ultraviolet photon activation tandem mass spectrometry (MS) at 69 nm (18 eV) was used to characterize mixtures of oligo-porphyrans, a class of highly sulfated oligosaccharides. Porphyrans, hybrid polymers whose structures are far from known, continue to provide a challenge for analytical method development. Activation by 18 eV photons led to a rich fragmentation of the oligo-porphyrans, with many cross-ring and glycosidic cleavages. In contrast to multistage MSn strategies such as activated electron photodetachment dissociation, a single step of irradiation by energetic UV of multiply charged anions led to a complete fragmentation of the oligo-porphyrans. In both ionization modes, the sulfate groups were retained on the backbone, which allowed the pattern of these modifications along the porphyran backbone to be described in unprecedented detail. Many structures released by the enzymatic degradation of the porphyran were completely resolved, including isomers. This work extends the existing knowledge of the structure of porphyrans. In addition, it provides a new demonstration of the potential of activation by high-energy photons for the structural analysis of oligosaccharides, even in unseparated mixtures, with a particular focus on sulfated compounds.


Fabrication of nanocrystal ink based superstrate-type CuInS₂ thin film solar cells.
A CuInS₂ (CIS) nanocrystal ink was applied to thin film solar cell devices with superstrate-type configuration. Monodispersed CIS nanocrystals were synthesized by a colloidal synthetic route and re-dispersed in toluene to form an ink. A spray method was used to coat CIS films onto conducting glass substrates. Prior to CIS film deposition, TiO₂ and CdS thin films were also prepared as a blocking layer and a buffer layer, respectively. We found that both a TiO₂ blocking layer and a CdS buffer layer are necessary to generate photoresponses in superstrate-type devices. The best power conversion efficiency (∼1.45%) was achieved by the CIS superstrate-type thin film solar cell device with 200 and 100 nm thick TiO₂ and CdS films, respectively.


Analogous Diamondene Nanotube Structure Prediction Based on Molecular Dynamics and First-Principle Calculations.
A concentric twin tube (CTT) can be built by placing a carbon nanotube (CNT) in another identical CNT. Different from diamondene nanotubes, a stable CTT has no inter-shell covalent bond. As a prestressed double-walled nanotube, CTT has a lower structural stability at a finite temperature. According to the molecular dynamics and first-principle calculations, (a) CTTs have three types of relaxed configurations. In a type III CTT, the inner tube buckles to produce a V-shaped cross-section, and the outer tube may be convex or concave. (b) The minimal radii of relaxed zigzag and armchair CTTs with concave outer tubes were found. (c) After relaxation, the circumferences and areas of the two tubes in a type III CTT are different from those of the corresponding ideal CNT. The area change rate (A-CR) and circumference change rate (C-CR) of the outer tube are the first-order Gaussian function of the radius of the ideal CNT (which forms the CTT), and tends to be 73.3% of A-CR or 95.3% of C-CR, respectively. For the inner tube of a CTT, the A-CR is between 29.3% and 37.0%, and the C-CR is close to 95.8%. (d) The temperature slightly influences the findings given above.


Revealing all: misleading self-disclosure rates in laboratory-based online research.
Laboratory-based experiments in online self-disclosure research may be inadvertently compromising the accuracy of research findings by influencing some of the factors known to affect self-disclosure behavior. Disclosure-orientated interviews conducted with 42 participants in the laboratory and in nonlaboratory settings revealed significantly greater breadth of self-disclosure in laboratory interviews, with message length and intimacy of content also strongly related. These findings suggest that a contrived online setting with a researcher presence may stimulate motivation for greater self-disclosure than would occur naturally in an online environment of an individual's choice. The implications of these findings are that researchers should consider the importance of experimental context and motivation in self-disclosure research.


War in Ukraine Disrupts Trials, Cancer Care.
The war in Ukraine is disrupting routine patient care, clinical trials, and basic cancer research-with potentially dire consequences. Physicians and researchers are helping patients as best they can, but cancer mortality is expected to rise in the country, and the impact on research could slow medical progress.


Ectopic Retrolaryngeal Parathyroid Adenoma Detected by 18F-Ethylcholine PET/US Fusion Imaging.
A 68-year-old woman was referred with the diagnosis of symptomatic pHPT (primary hyperparathyroidism). Ultrasonography (US) and 99mTc-MIBI scintigraphy could not clearly identify a parathyroid adenoma. A primary unilateral surgical exploration remained unsuccessful to remove adenomatous parathyroid tissue and the pHPT persisted. 18F-ethylcholine PET/CT showed a left-sided retropharyngeal lesion with intense tracer uptake that could not be detected on US images at first sight. Therefore, additional 18F-ethylcholine PET/US fusion imaging was performed and revealed a poorly definable nodular structure on US that could be unambiguously correlated to the PET finding. Surgical excision confirmed an oncocytic variant of parathyroid adenoma, and parathormone and calcium levels normalized immediately.


Ocular tuberculosis masquerading as atypical ocular toxoplasmosis.
Ocular tuberculosis is a great mimicker of various uveitis entities. We present a case of a 29-year-old male who came in with blurring of vision and floaters in the left eye. On examination, the left eye had anterior chamber cells and vitritis associated with retinitis. He had no other symptoms. The initial presentation was consistent with ocular toxoplasmosis, and he was started on oral sulfamethoxazole-trimethoprim and showed a good response to the treatment. However, work-up revealed negative toxoplasma antibody titers but a positive M. tuberculosis interferon-gamma release assay test and Mantoux test, making the diagnosis of ocular tuberculosis more likely. The patient was shifted to antituberculous therapy, which eventually resulted in the resolution of the inflammation with a recovery of the visual acuity. The diagnosis of ocular tuberculosis requires a detailed medical history as well as microbiologic and immunologic studies. A high index of suspicion by the treating ophthalmologist is necessary to reveal the diagnosis.


Teaching animal welfare in some veterinary schools in Latin America.
Animal welfare is an emerging topic in Latin America because of its impact on animal health, international trade, industry economic viability, and consumer perceptions. To enable veterinarians to be primary promoters of animal welfare, their training must include competencies in ethics, ethology, research, and public policy. During the past 10 years, animal welfare has gradually been incorporated into the curricula of several schools of veterinary medicine in Chile and other Latin American countries. Inclusion in these curricula is limited by a shortage of knowledgeable instructors. Research sustains inclusion of animal welfare in the curricula, but funding for research is often lacking.


Challenges of cardiac sarcoidosis.
Sarcoidosis is a multisystem granulomatosis of unknown origin, which can involve almost any organ. Most frequently the disease involves the lungs and mediastinal lymph nodes, but it can affect the skin, the eyes, nervous system, the heart, kidneys, joints, muscles, calcium metabolism, and probably any other anecdotical organ involvement. Cardiac sarcoidosis is one of the most challenging involvements, as it can lead to cardiac mortality and morbidity, and also because the diagnosis may be difficult. With no specific symptoms, cardiac sarcoidosis may be difficult to suspect in a patient with no previous extra-cardiac sarcoidosis diagnosis. This manuscript reviews the current knowledge of the diagnosis and decision to treat cardiac sarcoidosis, and illustrates the information with a case presentation of a young adult with no risk factors, no previous diagnosis of sarcoidosis, and with cardiac symptoms impairing his quality of life.


Clinical applications of carcinoembryonic antigen.
Although carcinoembryonic antigen (CEA) has been the subject of interest for many investigators for over 20 years, many questions still remain unanswered concerning the CEA molecule. These include the ultimate clinical potential of CEA as a tumor marker (specificity, sensitivity, distribution), the biological role of CEA, and the genetic control of CEA synthesis. Initially, much of the work with CEA concerned its physicochemical and immunochemical properties, as well as of cross-reacting molecules, and methods of serologic detection of CEA. More recent studies have focused on cloning of the CEA gene and genetic control of CEA production. An extensive literature exists concerning the role of serum CEA assays and their potential value in determining the prognosis and monitoring of patients affected with cancers of various organs. Despite extensive research into the biology of CEA, few papers deal with the application of CEA immunohistochemistry and immunocytochemistry as concerns normal cellular development, the degree of tumor anaplasia, and the various diagnostic problems of surgical pathology. There has also been a great deal of interest in the utility of both polyclonal and monoclonal antibodies to CEA both in the radioimmunolocalization and potential therapy of CEA-producing tumors. This review summarizes the past and current findings of the clinical applicability of the serum measurement of CEA and examines the status of radioimmunolocalization of tumors as a basis for effective antibody targeted immunotherapy in the future.


Role of non-RT1 genes in the response of rat lymphocytes to Mycoplasma arthritidis T cell mitogen, concanavalin A and phytohemagglutinin.
A comparison of splenic cells from various inbred rat strains indicated that DA, Lewis, Buffalo, August, Wistar Furth, and (LEW X BN)F1 all responded well to the Mycoplasma arthritidis T cell mitogen, phytohemagglutinin and concanavalin A, but cells from BN and MAXX rats were very weakly or nonresponsive. Cells from congenic strains expressing nonresponder background genes, and responder haplotypes at RT1 (BN.1L(LEW), RT1; BN.1A(DA), RT1av1) failed to respond significantly to the mitogens. Rats expressing responder background genes but the nonresponder haplotype at RT1 at RT1 (WF.1N-(MAXX), RT1n) exhibited high responses to all mitogens. The controlling role of non-RT1 genes was confirmed by testing tissue-typed (DA X BN)F2 progeny and (DA X BN)F1 X DA and (DA X BN)F1 X BN progeny. No association was seen between the expression of a/a, a/n, or n/n at RT1 and the degree of response to the mitogens. In contrast, as the proportion of DA non-RT1 genes increased, so did the degree of mitogenic responsiveness. Similar results were obtained by using a partially purified preparation of the mycoplasma T cell mitogen. The results indicated that in the (DA X BN)F1 hybrids, responsiveness to all mitogens was recessive: this contrasts with the (LEW X BN)F1 hybrids in which responsiveness was dominant. Finally, we showed that both responder and nonresponder splenic cells were capable of binding the M. arthritidis mitogen. The data contrast with those obtained with nonresponder mouse strains the cells of which failed to bind mitogen due to the absence of the E alpha chain of the I-E-coded molecule.


Longer-Term Effects of the Glycaemic Index on Substrate Metabolism and Performance in Endurance Athletes.
Nutrition has a decisive influence on athletic performance. However, it is not only the nutrient intake during exercise that is important, but the daily diet must also be adapted to the requirements of physical activity in order to optimally promote training adaptations. The goal of prolonged endurance training is to enhance fat oxidation, to maintain aerobic performance at a higher intensity while sparing limited carbohydrate stores. The targeted modification of macronutrient intake is a common method of influencing substrate metabolism, fuel selection, and performance. However, it is not well established whether the glycaemic index of carbohydrates in our daily diet can improve endurance performance by influencing carbohydrate or fat oxidation during training. Therefore, the aim of the following review is to elucidate the possible influence of the glycaemic index on substrate utilization during exercise and to clarify whether the consumption of a long-term high-carbohydrate diet with different glycaemic indices may have an influence on substrate metabolism and endurance performance.


A 63-Year-Old Woman With Progressive Dyspnea After Remission of Lymphoma.
A 63-year-old woman visited our hospital for a further evaluation of progressive dyspnea. She had developed a progressive airflow obstruction after 3 years' remission of non-Hodgkin's lymphoma (follicular mixed cell type), which had been treated with chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The patient's primary care physician had diagnosed her as having COPD and bronchial asthma and had treated her with medications including inhaled corticosteroids, tiotropium, and oral erythromycin. Her dyspnea had gradually worsened, however, and she had a score of 4 on the modified Medical Research Council dyspnea scale at the time of admission to our hospital.


Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendation.
Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed to construct a recommendation on the use of melatonin in children and adolescents aged 5-20 years with idiopathic chronic insomnia. A systematic search for guidelines, systematic reviews and randomised controlled trials (RCT) were performed in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A search for adverse events in otherwise healthy children and adolescents was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 18, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (5-20 years of age) with idiopathic chronic insomnia, in whom sleep hygiene practices have been inadequate and melatonin was tested. There were no restrictions on dosage, duration of treatment, time of consumption, or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, all-cause dropouts, and non-serious adverse events. Outcomes were assessed at different time points to assess short-term and long-term effects. Meta-analysis was performed using inverse variance random-effects model and risk of bias was assessed using Cochrane risk of bias tool. If possible, funnel plots would be constructed to investigate publication bias. Heterogeneity was calculated via I2 statistics. A multidisciplinary guideline panel formulated the recommendation according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was subsequently used to discuss the feasibility and acceptance of the constructed recommendation alongside the impact on resources and equity. The protocol is registered with the Danish Health Authority. We included eight RCTs with 419 children and adolescents with idiopathic chronic insomnia. Melatonin led to a moderate increase in total sleep time by 30.33 min (95% confidence interval (CI) 18.96-41.70, 4 studies, I2 = 0%) and a moderate reduction in sleep latency by 18.03 min (95% CI -26.61 to -9.44, 3 studies, I2 = 0%), both as assessed by sleep diary. No other beneficial effects were found. None of the studies provided information on serious adverse events, yet the number of participants experiencing non-serious adverse events was increased (Relative risk 3.44, 95% CI 1.25-9.42, 4 studies, I2 = 0%). Funnel plots were not constructed due to the low number of studies. The certainty of evidence was very low on the quality of sleep and low for daytime functioning. Evidence of very low certainty shows that benefits are limited and unwanted events are likely when melatonin is used to treat otherwise healthy children and adolescents with chronic insomnia. Melatonin should never be the first choice of treatment for this particular population, yet carefully monitored short-term use may be considered if sleep hygiene practices and non-pharmacological interventions have proven inadequate, and only if daytime function is compromised. The Danish Health Authority and the Parker Institute, Bispebjerg and Frederiksberg Hospital supported by the Oak Foundation.


Osteoconductive properties and efficacy of resorbable bioactive glass as a bone-grafting material.
The height of the available bone between the alveolar ridge and the sinus is often insufficient for placing endosseous implants in the posterior maxilla. Subantral augmentation after sinus elevation can be performed using bone-grafting materials such as autogenous bone, allografts, and alloplasts. The properties and performance of a recently developed resorbable bioactive glass (BioGran) were investigated with regard to bioactivity and bone-forming capability. The bioactive glass was grafted into the sinus cavities of 25 patients and biopsies were taken after 7 months. The samples were examined by conventional histologic techniques, elemental composition and distribution assayed by an electron probe microanalyzer, and comparative biomechanical data for BioGran and bone tissue gathered. Histologic and biomechanical examination indicated bone formation in all cases, with biomechanical properties of the regenerated bone close to those of bone tissue. The results of this study suggest that BioGran exhibits osteoconductive properties and efficacy as an alloplastic bone-grafting material.


Pneumonia-Induced Inflammation, Resolution and Cardiovascular Disease: Causes, Consequences and Clinical Opportunities.
Pneumonia is inflammation in the lungs, which is usually caused by an infection. The symptoms of pneumonia can vary from mild to life-threatening, where severe illness is often observed in vulnerable populations like children, older adults, and those with preexisting health conditions. Vaccines have greatly reduced the burden of some of the most common causes of pneumonia, and the use of antimicrobials has greatly improved the survival to this infection. However, pneumonia survivors do not return to their preinfection health trajectories but instead experience an accelerated health decline with an increased risk of cardiovascular disease. The mechanisms of this association are not well understood, but a persistent dysregulated inflammatory response post-pneumonia appears to play a central role. It is proposed that the inflammatory response during pneumonia is left unregulated and exacerbates atherosclerotic vascular disease, which ultimately leads to adverse cardiac events such as myocardial infarction. For this reason, there is a need to better understand the inflammatory cross talk between the lungs and the heart during and after pneumonia to develop therapeutics that focus on preventing pneumonia-associated cardiovascular events. This review will provide an overview of the known mechanisms of inflammation triggered during pneumonia and their relevance to the increased cardiovascular risk that follows this infection. We will also discuss opportunities for new clinical approaches leveraging strategies to promote inflammatory resolution pathways as a novel therapeutic target to reduce the risk of cardiac events post-pneumonia.


Tetranuclear lanthanide-based silsesquioxanes: towards a combination of a slow relaxation of the magnetization and a luminescent thermometry.
Lanthanide-based silsesquioxanes constitute an emerging family of cage-like metallasilsesquioxanes with exciting optical and magnetic properties. We report here the synthesis, structures and luminescence properties of a series of tetranuclear lanthanide-silsesquioxane compounds of general formula [NEt4]2[(Ph4Si4O8)2(Ln/Ln')4(NO3)6(EtOH)2(MeCN)2]·4(MeCN) with different lanthanide ions (where Ln/Ln' = Dy3+/Eu3+ (1), Dy3+/Tb3+ (2) and Eu3+/Tb3+/Y3+ (3)) and investigate the impact of the lanthanide ions combination on magnetic and photo-luminescent properties. Compound 1 behaves as a field-induced Single Molecule Magnet (SMM) and presents temperature-dependent luminescence characteristics of Eu3+ making it an emissive thermometer working in the temperature range 293-373 K with the maximum relative sensitivity of 1.15% K-1 achieved at 293 K. Compounds 2 and 3 are paramagnets, which demonstrate a characteristic photoluminescence with Dy3+ to Tb3+ and Tb3+ to Eu3+ energy transfers, respectively.


Escin Sodium Improves the Prognosis of Acute Pancreatitis via Promoting Cell Apoptosis by Suppression of the ERK/STAT3 Signaling Pathway.
Acute pancreatitis (AP), an inflammatory disorder of the pancreas, can cause systemic inflammatory responses. Escin Sodium (ES), a natural mixture of triterpene saponins extracted from the dry ripe fruit of Fructus Aesculi or horse chestnut crude, has been demonstrated to have antiedematous, anti-inflammatory, and antiexudative effects. We here aim to investigate the effects of ES pretreatment on AP in vivo and in vitro and explore its potential molecular mechanism. In the present study, we demonstrated that ES pretreatment could apparently decrease amylase and lipase, downregulate inflammatory cytokines, and attenuate pancreatic damage. Additionally, the increased expression of apoptotic-related proteins and the results of flow cytometry demonstrated the effects of ES on promoting apoptosis in acinar cells. Moreover, ES could enhance mitochondrial membrane potential (MMP, ΔΨm) and reactive oxygen species (ROS) level and reduce intracellular calcium concentration, which are closely related to mitochondrial-mediated death. The effect of ES pretreatment on acinar cell apoptosis was furtherly confirmed by the regulatory pathway of the ERK/STAT3 axis. These results suggest that ES attenuates the severity of AP by enhancing cell apoptosis via suppressing the ERK/STAT3 signaling pathway. These findings provide evidence for ES which is treated as a novel and potent therapeutic for the treatment of AP.


Management of acute childhood diarrhoea in Saudi Arabia: practices versus the WHO recommendations.
The fluid management of 247 infants and children who were admitted to King Fahad Hospital at Al Baha, Saudi Arabia with acute diarrhoea was reviewed. Half of them were infants and 25% were exclusively breast fed. Although dehydration was mild in 149 (60.3%) patients and 227 (92.7%) were at the most moderately dehydrated, as many as 95.8% were given intravenous (IV) hydration at least initially. This indicates that the WHO recommendation to prescribe oral rehydrating solution (ORS) for the control of diarrhoeal diseases, is still not implemented at some of the regional hospitals in Saudi Arabia, and emphasizes the need for urgent and effective efforts to rectify this situation.


Specific phosphorylation at serine-283 of alpha tropomyosin from frog skeletal and rabbit skeletal and cardiac muscle.
Tropomyosin, extracted from the leg muscle of frogs that had been injected with [32P]orthophosphate, was fractionated into two components, alpha and beta, on a CM-cellulose column. Radioactivity was associated only with the alpha component. A single phosphorylation site was located at serine-283 (pentultimate at the COOH-terminal end) of the frog alpha tropomyosin. The same phosphorylated peptide was recovered in low yields from both rabbit skeletal alpha and cardiac tropomyosin. The presence of covalently bound phosphate in alpha tropomyosin and its absence in the beta component of rabbit skeletal muscle was suggested by 31P NMR spectroscopy. The amino acid sequences around the phosphorylation sites of frog and rabbit tropomyosin are identical. Because this sequence is not similar to any other known phosphorylation site in proteins, this indicates the existence of either specific kinase or phosphatase that can distinguish between alpha and beta tropomyosins. In a model proposed for the head-to-tail overlap of alpha tropomyosin molecules, one O-phosphoserine-283 residue could form a salt linkage with lysine-6 on one side of the overlap region and another with lysine-12 on the other side. This would predict a difference in the stability of polymers of phosphorylated and nonphosphorylated alphaalpha and alphabeta dimers of tropomyosin.


miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis.
Coronary microembolization (CME) commonly develops as a complication after percutaneous coronary intervention (PCI), and associated inflammation is a leading driver of myocardial damage. Cardiomyocyte loss in the context of ischemic myocardial disease has been linked to inflammatory pyroptotic cell death. Additionally, miR-200a-3p dysregulation has been linked to myocardial ischemia-reperfusion and many other pathological conditions. However, how miR-200a-3p impacts cardiomyocyte pyroptosis in the context of CME remains to be assessed. Herein, a rat model of CME was established via the injection of microembolic spheres into the left ventricle. When myocardial tissue samples from these rats were analyzed, miR-200a-3p levels were markedly decreased, whereas thioredoxin-interacting protein (TXNIP) levels were increased. The ability of miR-200a-3p to directly target TXNIP and to control its expression was confirmed via dual-luciferase reporter assay. Adeno-associated virus serotype 9-pre-miR-200a-3p (AAV-miR-200a-3p) construct transfection was then employed as a means of upregulating this miRNA in CME model rats. Subsequent assays, including echocardiography, enzyme-linked immunosorbent assays (ELISAs), hematoxylin-eosin (H&E) staining, hematoxylin-basic fuchsin-picric acid (HBFP) staining, TdT-mediated dUTP nick-end labeling (TUNEL) staining, immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting revealed that miR-200a-3p overexpression inhibited cardiomyocyte pyroptosis and alleviated CME-induced myocardial injury by inhibiting the TXNIP/NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathway. The ability of miR-200a-3p to protect against CME-induced myocardial injury thus highlights a novel approach to preventing or treating such myocardial damage in clinical settings.


Activation mechanisms of the first sphingosine-1-phosphate receptor.
Activation of the first sphingosine-1-phosphate receptor (S1PR1 ) promotes permeability of the blood brain barrier, astrocyte and neuronal protection, and lymphocyte egress from secondary lymphoid tissues. Although an agonist often activates the S1PR1 , the receptor exhibits high levels of basal activity. In this study, we performed long-timescale molecular dynamics and accelerated molecular dynamics (aMD) simulations to investigate activation mechanisms of the ligand-free (apo) S1PR1 . In the aMD enhanced sampling simulations, we observed four independent events of activation, which is characterized by close interaction between Y3117.53 and Y2215.58 and increased distance between the intracellular ends of transmembrane (TM) helices 3 and 6. Although TM helices TM3, TM6, TM5 and, TM7 are associated with GPCR activation, we discovered that their movements are not necessarily correlated during activation. Instead, TM5 showed a decreased correlation with each of these regions during activation. During activation of the apo receptor, Y2215.58 and Y3117.53 became more solvated, because a water channel formed in the intracellular pocket. Additionally, a lipid molecule repeatedly entered the receptor between the extracellular ends of TM1 and TM7, providing important insights into the pathway of ligand entry into the S1PR1 .


[Ovulation induction with human menopausal gonadotropins in hypothalamic-hypophyseal disfunction].
This is a report on the institutional experience of the use of Human Menopausal Gonadotropins (HMG) in anovulatory women diagnosed as hypothalamic-hypophysiary dysfunction of Group II of WHO with previous failure to chlomifen citrate therapy. In a period of three years 180 patients were gathered with 420 cycle of treatment, obtaining ovulation in 340 cycles (81%). The ovarian hyperstimulation syndrome (OHS) was present in 15 cases (3.5%). There were 115 pregnancies that correspond to 33.8% of oculatory cycles and to 63.8% of the amount of patients. Multiple pregnancy incidence was 10.4%, and the gestational loses rate was 26%; these results are similar to what has been reported in literature. It is concluded that this medication is a good option of treatment for this type of patients, provided that there are the necessary means to expert and adequate surveillance.


Angular momentum and cross sections for fusion with weakly bound nuclei: breakup, a coherent effect.
Results for the cross section and average angular momentum for complete fusion at energies around the Coulomb barrier are presented for 7Li with 165Ho. Comparison of the cross sections with a one-dimensional barrier penetration model, using a potential consistent with the measured elastic scattering, showed a reduction above the barrier and an enhancement below it. An increase in the measured average angular momentum, <l>, above the barrier and its consistency with that obtained from the fusion excitation function for weakly bound nuclei, is reported. These results together with a reanalysis of existing data conclusively demonstrate that the effect of breakup on fusion is coherent, like coupling to any nonelastic channel.


Lumbar developmental malformation: intertransverse pseudarthrosis.
Developmental malformations of lumbar transverse processes commonly include hypertrophy of the transverse process, overgrowth of the transverse process, and persistence of the transverse process epiphysis. To date, the intertransverse pseudarthrosis malformation has not been reported. In this case report, we identified a case of intertransverse pseudarthrosis through X-ray imaging, which was confirmed by CT scanning. And intertransverse pseudarthrosis of spine was proved by Surgery.


Magic angle spinning magnetic resonance: a novel method opening up translational research into NAFLD?
NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis) are of increasing importance, both in connection with insulin resistance and with the development of liver cirrhosis. Histological samples are still the 'gold standard' for diagnosis; however, because of the risks of a liver biopsy, non-invasive methods are needed. MAS (magic angle spinning) is a special type of NMR which allows characterization of intact excised tissue without need for additional extraction steps. Because clinical MRI (magnetic resonance imaging) and MRS (magnetic resonance spectroscopy) are based on the same physical principle as NMR, translational research is feasible from excised tissue to non-invasive examinations in humans. In the present issue of Clinical Science, Cobbold and co-workers report a study in three animal strains suffering from different degrees of NAFLD showing that MAS results are able to distinguish controls, fatty infiltration and steatohepatitis in cohorts. In vivo MRS methods in humans are not obtainable at the same spectral resolution; however, know-how from MAS studies may help to identify characteristic changes in crowded regions of the magnetic resonance spectrum.


A patient-specific numerical model of the ankle joint for the analysis of contact pressure distribution.
A patient-specific numerical model of the ankle joint has been developed using open-source software with realistic material properties that mimics the physiological movement of the foot during the stance phase of the gait cycle. The patient-specific ankle geometry has been segmented as a castellated surface using 3DSlicer from the computed tomography image scans of a subject with no congenital or acquired pathology; subsequently, the bones are smoothed, and cartilage is included as a uniform thickness extruded layer. A high-resolution Cartesian mesh has been generated using cfMesh. The material properties are assigned in the model based on the CT image Hounsfield intensities and compared to a sandwich-based material model. Gait data of the same subject was obtained and used to relatively position the tibia, talus, and calcaneus bones in the model. The stance phase of the gait cycle is simulated using a cell-centred finite-volume method implemented in open-source software OpenFOAM. The predicted peak contact pressures occur in the range of 4.85-5.53 MPa with average pressures in the range of 1.56-1.95 MPa, and the contact area ranges between 429 and 707.8 mm2 for the entire stance phase with the mid-stance phase predicting the maximum contact area. These predictions are in agreement with results from the literature. The effect of arthritis on the contact characteristics of the ankle joint has also been examined. A concentrated increase in pressure was predicted that could be manifested as pain, thereby leading to reduced motion in the ankle. The model, with continued development, has the capability to understand the effect of joint degradation and furthermore, could help provide a tool to predict the efficiency of therapeutic surgical procedures as well as guide the development of next generation ankle prostheses. The work would be made available in the University College Dublin depository (https://github.com/laxmimurali/anklejoint) as well as research gate once the article has been published.


Biodegradation of phenol in batch culture by pure and mixed strains of Paenibacillus sp. and Bacillus cereus.
The bacterial strains, Paenibacillus sp. (AY952466) and Bacillus cereus (DQ002384), have proven capacity to degrade lignin and pentachlorophenol. In the present study, both strains were screened at different concentrations of phenol on mineral salt agar medium in the presence of glucose. At optimized condition (pH 7.5 +/- 0.2, 37 +/- 1 degrees C, 120 rpm, 1% glucose w/v), it was observed that both Paenibacillus sp., B. cereus and its mixed culture degraded phenol (500 mg/l) up to 53.86%, 91.63% and 67.76% within 168 h of incubation, respectively. Phenol degradation was routinely monitored spectrophotometrically and further confirmed by HPLC. Catechol and 2-hydroxy muconic semialdehyde were identified as intermediate products from degraded samples using GC-MS. It was also observed that, in the absence of glucose, bacterial strains were unable to utilize phenol indicating the phenomenon of co-metabolism.


Repetitive behavior and restricted interests in young children with autism: comparisons with controls and stability over 2 years.
Restricted, repetitive and stereotyped patterns of behavior, interests and activities [RRBs] are among the core symptoms of autism spectrum disorders (ASD). Previous studies have indicated that RRBs differentiate ASD from other developmental disorders and from typical development. This study examined the presentation of RRBs as reported on the Repetitive Behavior Scale-Revised, a caregiver report, in children with ASD [separated into autism and Pervasive Developmental Disorder-Not Otherwise Specified groups] compared with children with nonspectrum developmental delays or typical development. We examined the role of age, cognitive functioning, sex and social communication impairment as they relate to RRBs. The stability of RRBs in children with autism was also examined over the course of 2 years. Results of the study confirmed that the amount and type of RRBs differs by diagnosis. Age, cognitive functioning, sex and social-communication impairment were not significant correlates. Among children with autism, RRBs remained stable over time.


Insomnia is a frequent finding in adults with Asperger syndrome.
Asperger syndrome (AS) is a neurodevelopmental disorder belonging to autism spectrum disorders with prevalence rate of 0,35% in school-age children. It has been most extensively studied in childhood while there is scarcity of reports concerning adulthood of AS subjects despite the lifelong nature of this syndrome. In children with Asperger syndrome the initiation and continuity of sleep is disturbed because of the neuropsychiatric deficits inherent of AS. It is probable that sleep difficulties are present in adulthood as well. Our hypothesis was that adults with AS suffer from difficulty in initiating and maintaining sleep and nonrestorative sleep (insomnia). 20 AS without medication were compared with 10 healthy controls devoid of neuropsychiatric anamnesis. Clinical examination, blood test battery and head MRI excluded confounding somatic illnesses. Structured psychiatric interview for axis-I and axis-II disorders were given to both groups as well as Beck Depression Inventory and Wechsler adult intelligence scale, revised version.Sleep quality was assessed with sleep questionnaire, sleep diary during 6 consecutive days and description of possible sleep problems by the participants own words was requested. compared with controls and with normative values of good sleep, AS adults had frequent insomnia. In sleep questionnaire 90% (18/20), in sleep diary 75% (15/20) and in free description 85% (17/20) displayed insomnia. There was a substantial psychiatric comorbidity with only 4 AS subject devoid of other axis-I or axis-II disorders besides AS. Also these persons displayed insomnia. It can be noted that the distribution of psychiatric diagnoses in AS subjects was virtually similar to that found among patient with chronic insomnia. the neuropsychiatric deficits inherent of AS predispose both to insomnia and to anxiety and mood disorders. Therefore a careful assessment of sleep quality should be an integral part of the treatment plan in these individuals. Conversely, when assessing adults with chronic insomnia the possibility of autism spectrum disorders as one of the potential causes of this condition should be kept in mind.


Child Salivary SIgA and Its Relationship to Enteric Infections and EED Biomarkers in Maputo, Mozambique.
Characterizing child immunological responses to enteric infections with antibody detection in serum can be challenging in resource-constrained field settings, because sample collection requires trained individuals and its invasive procedure may lead to low response rates, especially among children. Saliva may present a promising non-invasive alternative. The objectives of this research were to compare salivary antibody levels in children to enteric infections and biomarkers of environmental enteric dysfunction (EED). We collected saliva samples from children aged one to six years enrolled in a sanitation trial in Maputo, Mozambique, and characterized salivary secretory immunoglobulin A (SIgA) concentrations with enzyme-linked immunosorbent assays. We used multilevel linear models to analyze cross-sectional associations between salivary SIgA and the number of concurrent enteric pathogen infections, as well as EED biomarkers in matched stool samples. Median salivary SIgA concentrations in this study population were 54 μg/mL (inter-quartile range (IQR): 34, 85 μg/mL), and SIgA levels were similar between children of different ages. SIgA was lower in children experiencing a higher number of concurrent infections -0.04 log μg/mL (95% confidence interval (CI): -0.08 to -0.005 log μg/mL), but was not associated with any of the included EED biomarkers. Contrary to evidence from high-income countries that suggests salivary SIgA increases rapidly with age in young children, the high prevalence of enteric infections may have led to a suppression of immunological development in this study sample and could in part explain the similar SIgA levels between children of different ages.


Tumor necrosis factor-α-induced protein 8-like 2 alleviates morphine antinociceptive tolerance through reduction of ROS-mediated apoptosis and MAPK/NF-κB signaling pathways.
Chronic morphine tolerance is a repulsive barrier to the clinical treatment of pain. Whereas the underlying molecular mechanisms of morphine tolerance remain unknown. Here, we proposed that tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is an essential control point regarding the progression of chronic morphine antinociceptive tolerance. We found that TIPE2 levels in the lumbar spinal cord were significantly downregulated in the morphine tolerance mouse model. Specifically, decreased TIPE2 by morphine tolerance was primarily expressed in spinal neurons, while increased expression of spinal TIPE2 distinctly attenuated the chronic morphine antinociceptive tolerance and tolerance-associated hyperalgesia. We also observed that increased expression of spinal TIPE2 significantly reduced morphine tolerance-induced neuronal ROS production and apoptosis, along with the activation of MAPKs and NF-κB signaling pathways. Moreover, the increased TIPE2 expression inhibited neuronal activation and glial reactivity in the spinal dorsal horn after chronic morphine exposure. Additionally, TIPE2 overexpression in cultured SH-SY5Y cells significantly suppressed ROS production and apoptosis in response to morphine challenge. Therefore, we can conclude that the upregulation of spinal TIPE2 may attenuate the morphine antinociceptive tolerance via TIPE2-dependent downregulation of neuronal ROS, inhibition of neuronal apoptosis, suppression of MAPKs and NF-κB activation. TIPE2 may be a potential strategy for preventing morphine tolerance in the future studies and clinical settings.


Screening and evaluation of chronic and occult Hepatitis B in chemo - radiotherapy patients with cancer.
Hepatitis B virus infection (HBV) and its complications is one of the most serious problems of the health system in many parts of the world. In the present study, we will assess chronic and occult HBV and isolated anti-Hepatitis B core antigen whose screening and evaluation is not routine in different populations. This descriptive analytical study was conducted on 213 patients undergoing chemotherapy - radiotherapy referred to the hematology - oncology clinics of Isfahan, Iran in 2012. In order to determine the serum levels of hepatitis B surface antigen (HbSAg), Hepatitis B Antigen and Antibody (HBCAb), aspartate aminotransferase (AST), alanine transaminase (ALT) and Alkaline phosphatase (ALK.P), venous blood samples were obtained. If the HBCAb sample was positive, another sample of the serum was sent to the laboratory to perform polymerase chain reaction and to determine viral load. The mean age of the patients was 47.7 ± 9 years, with an age range of 27 -73 years; 98 (46%) and 115 (54%) cases were male and female, respectively, with mean age of 51.9 ± 8.3 and 44.1 ± 8.1 years, and there was no significant difference (P < 0.001). The mean level of liver enzymes including AST, ALT and ALK.P were 34.2 ± 36.02, 38.9 ± 47.1 and 252.1 ± 234.7, respectively. Two cases were HbSAg positive (0.9%) and six cases were HBCAb positive (2.8%) and HbSAg negative. Three cases had a high viral load at the rate of starting treatment among positive anti-HBC patients. Because occult hepatitis is investigated less commonly in routine studies, it seems that screening and evaluating its prevalence is useful in the management of patients.


Genomic manipulations in alkaliphilic haloarchaea demonstrated by a gene disruption in Natrialba magadii.
Alkaliphilic haloarchaea, a distinct physiological group from the closely related neutrophilic haloarchaea, represent an underutilized resource for basic research and industrial applications. In contrast to the neutrophilic haloarchaea, no reports on genomic manipulations in haloalkaliphiles have been published until now. Genomic manipulations via homologous recombination are useful for basic research. In this study, we demonstrate the possibility for this strategy in alkaliphilic haloarchaea for the first time. In a previous study, we developed a PEG-mediated transformation technique for alkaliphilic haloarchaea that was deployed in this study to deliver a gene disruption cassette into the model organism Natrialba magadii. The gene encoding for the well-studied Natrialba extracellular protease was successfully disrupted by a recombination marker gene, demonstrating a proof of principle for the usability of homologous recombination for genomic manipulations in alkaliphilic haloarchaea. Since halo(alkali)philic Archaea are polyploid, a selection process was applied in order to obtain a mutant strain containing exclusively disrupted genes. The resulting strain exhibited no proteolytic activity measurable by an azo-casein assay. Complementation was able to restore proteolytic activity. The expression pattern of the Natrialba extracellular protease was different in the complemented strain.


Microencapsulation of hydroxyzine HCl by thermal phase separation: in vitro release enhancement and in vivo pharmacodynamic evaluation.
The systemic effect of hydroxyzine hydrochloride following its oral administration or topical application is associated with non compliant anticholinergic effect. Subsequently, the present study aims to prepare microcapsules loaded with hydroxyzine hydrochloride enabling its controlled release into the skin and reducing the side effect of its systemic absorption. The microcapsules were prepared by thermal phase separation method using ethyl cellulose/cyclohexane. Optimization of the formulation parameters was carried out by: (1) varying the type and the concentration of the coacervation inducer with microcapsules prepared with three different core: wall ratios, (2) by using ethyl cellulose with two different viscosities, (3) and by the addition of pore inducers such as pregelatinized starch and sucrose in order to enhance the drug release. Microcapsules of 99% encapsulation efficiency were prepared using 1% w/v polyisobutylene, and 1:0.1 core: wall ratio. The highest percent of drug is released after 9 h from microcapsules prepared using 1:0.1 core :wall ratio. Almost 100% drug was released after 3 h, from the same microcapsules prepared with pregelatinized starch that acts as a core coated with the drug. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.


Delayed presentation of traumatic diaphragmatic rupture with tension colothorax and strangulation of the transverse colon.
A 26-year-old man presented to emergency department with respiratory distress. The initial diagnosis after chest X-ray was massive haemothorax, after insertion of a chest drain and further investigations, it turned up to be a rare case of a delay presentation of traumatic diaphragmatic rupture (DR) (after 1 year of the initial trauma). After excessive resuscitation of the patient in the emergency department, the patient underwent an emergency laparotomy which revealed ischaemic transverse colon herniated into the chest through a 7 cm diaphragmatic defect. Resection of the ischaemic bowel had been done, and the patient admitted to Intensive Therapy Unit (ITU) postoperatively. The patient had an uneventful recovery and discharged home on postoperative day 9. As DR after thoracoabdominal trauma is a rare condition that can be missed at initial presentation, we would like to highlight the main challenges in diagnosing and managing similar cases after reviewing related cases in the literature.


Using wearable technology to prevent pressure injuries: An integrative review.
Hospital-acquired pressure injuries (HAPIs) are a significant problem for hospitals worldwide, negatively affecting patients and organizations by decreasing quality of life and increasing organizational cost of care and workload. A common pressure injury prevention intervention is frequent turning, though compliance can be low. As a newer technology, wearable sensors have emerged as an intervention to increase turn compliance. The aim of this integrative review was to determine the clinical outcomes of using wearable sensors as a HAPI prevention intervention. This integrative review was appraised by two independent reviewers using the Johns Hopkins Nursing Evidence-Based Practice Research Appraisal Tool. Eleven articles were included. The use of wearable sensors increases compliance with frequent turn protocols while decreasing HAPIs and reducing organizational costs. Despite this, the use of such technology was not found to increase the quality of turns. Although staff who used this technology reported positive feedback, technological training is needed to ensure proper use of the sensors. This innovation has the potential to transform how nursing staff prevent pressure injuries, but more research is needed to definitively state whether wearable sensors will be efficacious as a pressure injury prevention intervention.


Experimental investigation of the penetration of ultrasound nanobubbles in a gastric cancer xenograft.
Nanobubbles as a type of ultrasound contrast agent have attracted much interest in recent years due to their many advantages, such as strong penetrating power and high stability. However, there is still insufficient morphological evidence concerning gas-filled nanobubbles in tumor tissue spaces and tumor angiogenesis. We used a gastric cancer xenograft as an example to study this question. Nanobubbles with a particle size of 435.2 ± 60.53 nm were prepared and compared with SonoVue® microbubbles in vitro and in vivo, and they exhibited a superior contrast imaging effect. After excluding the impact of the nanobubbles in blood vessels through saline flush, we used an ultrasound burst and frozen sectioning to investigate the distribution of nanobubbles in the gastric cancer xenografts and confirmed this by transmission electron microscopy. Preliminary results showed that the nanobubbles were able to pass through the gaps between the endothelial cells in the tumor vascular system to enter the tissue space. These findings could provide morphological evidence for extravascular ultrasound imaging of tumors and serve as a foundation for the application of nanobubbles in extravascular tumor-targeted ultrasonic diagnostics and therapy.


In Situ Electrochemical Generation of Reactive Chlorine Species for Efficient Ultrafiltration Membrane Self-Cleaning.
Reactive membranes based on hydroxyl radical generation are hindered by the need for chemical dosing and complicated module and material design. Herein, we utilize an electrochemical approach featuring in situ generation of reactive (radical) chlorine species (RCS) through anodization of chloride ions for membrane self-cleaning. A hybridized carbon nanotube (CNT)-functionalized ceramic membrane (h-CNT/CM), possessing high hydrophilicity, permeability, and conductivity, was fabricated. Using carbamazepine (CBZ) as a probe, we confirmed the presence of RCS in the electrified h-CNT/CM. The rapid and complete degradation of CBZ in a single-pass ultrafiltration indicates a high localized RCS concentration within the three-dimensional porous CNT interwoven layer. We further demonstrate that the electrogeneration of RCS is a critical prestep for free chlorine (HClO and ClO-) formation. The self-cleaning efficiency of the membrane after fouling with a model organic foulant (alginate) was assessed using an electrified cross-flow membrane filtration system. The fouled h-CNT/CM exhibits a near complete water flux recovery following a short (1 min) self-cleaning with an applied voltage of 3 or 4 V and feed solutions of 100 or 10 mM sodium chloride, respectively. Considering the superior performance of the RCS-mediated self-cleaning compared to conventional membrane chemical cleaning using sodium hypochlorite, our results exemplify an effective strategy for in situ electrogeneration of RCS to achieve a highly efficient membrane self-cleaning.


Microsatellite analysis of genetic diversity and population structure of Arabian horse populations.
The Arabian horse ignites imagination throughout the world. Populations of this breed exist in many countries, and recent genetic work has examined the diversity and ancestry of a few of these populations in isolation. Here, we explore 7 different populations of Arabians represented by 682 horses. Three of these are Middle Eastern populations from near the historical origin of the breed, including Syrian, Persian, and Saudi Arabian. The remaining Western populations are found in Europe (the Shagya Arabian and Polish Arabian) and in America (American Arabian). Analysis of genetic structure was carried out using 15 microsatellite loci. Genetic distances, analysis of molecular variance, factorial correspondence analysis, and a Bayesian method were applied. The results consistently show higher level of diversity within the Middle Eastern populations than the Western populations. The Western Arabian populations were the main source among population variation. Genetic differentiation was not strong among all Middle Eastern populations, but all American Arabians showed differentiation from Middle Eastern populations and were somewhat uniform among themselves. Here, we explore the diversities of many different populations of Arabian horses and find that populations not from the Middle East have noticeably lower levels of diversity, which may adversely affect the health of these populations.


Relationships among anxious symptomatology, anxiety sensitivity and laboratory pain responsivity in children.
Existing laboratory-based research in adult samples has suggested that anxiety sensitivity (AS) increases an individual's propensity to experience pain-related anxiety, which in turn enhances pain responsivity. Such relationships have not been examined in younger populations. Thus, the present study used structural equation modeling (SEM) to test a conceptual model in which AS would evidence an indirect relationship with pain intensity via its contribution to state-specific anticipatory anxiety in relation to a variety of laboratory pain tasks (cold pressor, thermal heat, and pressure pain) in 234 healthy children (116 girls; mean age = 12.6 years, range = 8-18 years). The model further hypothesized that existing anxious symptomatology would demonstrate a direct relationship with pain intensity. Results of the SEM supported the proposed conceptual model with the total indirect effect of AS accounting for 29% of the variance in laboratory pain intensity via its effects on pain-related anticipatory anxiety. AS did not however, evidence a direct relationship with pain intensity. Anxious symptomatology on the other hand, demonstrated a significant direct effect on pain intensity, accounting for 15% of variance. The combined effects of AS, anxiety symptoms, and anticipatory anxiety together explained 62% of the variance in pain intensity. These relationships did not differ for boys and girls, indicating no moderating effect of sex in the proposed model. The present results support the potential benefit of assessing both AS and anxiety symptoms in children prior to undergoing painful stimulation.


Research and commentary.
Background Families' experiences at the end of life are affected by the quality of care family and child receive. Parental voices are an important element of gathering information on caring experiences and quality issues.


Intervention to increase screening mammography among women 65 and older.
This paper reports the results of a practice-based intervention program to increase mammography screening among women 65 and older who receive their health care in the private sector. Forty-three primary-care practices and 2147 women in central and western North Carolina were enrolled in the study, and 1911 women completed all phases of the study. The intervention was a three-stage educational and counseling program designed to become progressively more intensive at each stage. The interventions included provider education in the form of current information on issues in mammography for older women, simply written educational materials on breast cancer and screening mailed to women, and a brief telephone counseling session for the women. While the analysis revealed no overall effect across all three stages of the intervention program, tests for interaction indicated a significant program effect for women who were 80 or older, had less than 9 years of education, were black, or had no private insurance to supplement Medicare. The results suggested that providing primary-care physicians with information on screening older women and providing the women with useful educational materials can increase participation in screening mammography among subgroups of women currently least likely to receive mammography screening.


The protective effect of immunoglobulin in murine tuberculosis is dependent on IgG glycosylation.
Antibodies have demonstrated having a protective effect in animal models of tuberculosis (TB). These experiments have considered the specificity of antigen recognition and the different isotypes and subclasses as significant contributors of this effect. However, the carbohydrate chain heterogeneity on the Fc region of IgG (Fc-IgG) can play an important role in modulating the immune response. Patients with TB usually have high titers of specific IgG; however, the carbohydrate associated with Fc-IgG usually lacks galactose. To assess the effect of this abnormal IgG in murine pulmonary TB, we evaluated the specificity of recognition to Mycobacterium tuberculosis antigens in vitro and protective effects in vivo comparing human intravenous immunoglobulin (IVIg) and IVIg treated with an endoglycosidase to remove the glycan residues (EndoS-treated IVIg). Our results showed similar antigen recognition. The study of distribution and kinetics of IVIg in serum and bronchial lavage after intraperitoneal (i.p.) administration in mice showed that IVIg circulates for 21 days. Finally, the protective effect of intact and EndoS-treated IVIg administered by i.p was studied in a murine model of progressive TB. IVIg treatment caused reduction in pulmonary bacilli loads, larger granulomas, and less pneumonia, while animals treated with EndoS-treated IVIg were not protected compared with control animals. Thus, IVIg has a protective activity in experimental pulmonary TB, and this effect requires intact Fc oligosaccharides.


Impaired Dual-Specificity Protein Phosphatase DUSP4 Reduces Corticosteroid Sensitivity.
We have reported that phosphorylation of the glucocorticoid receptor (GR) at Ser226 reduces GR nuclear translocation, resulting in corticosteroid insensitivity in patients with severe asthmas. A serine/threonine protein phosphatase 2A, which regulates c-Jun N-terminal kinase (JNK) 1 and GR-Ser226 signaling, is involved in this mechanism. Here, we further explored protein kinase dual-specificity phosphatases (DUSPs) with the ability to dephosphorylate JNK, and identified DUSP4 as a phosphatase involved in the regulation of corticosteroid sensitivity. The effects of knocking down DUSPs (DUSP1, 4, 8, 16, and 22) by small interfering RNA (siRNA) were evaluated in a monocytic cell line (U937). Corticosteroid sensitivity was determined by dexamethasone enhancement of FK506-binding protein 51 or inhibition of tumor necrosis factor α (TNFα)-induced interferon γ and interleukin 8 expression and GR translocation from cell cytoplasm to nucleus. The nuclear/cytoplasmic GR, phosphorylation levels of GR-Ser226 and JNK1, coimmunoprecipitated GR-JNK1-DUSP4, and DUSP4 expression were analyzed by western blotting and/or imaging flow cytometry. Phosphatase activity of immunoprecipitated (IP)-DUSP4 was measured by fluorescence-based assay. Knockdown of DUSP4 enhanced phosphorylation of GR-Ser226 and JNK1 and reduced GR nuclear translocation and corticosteroid sensitivity. Coimmunoprecipitation experiments showed that DUSP4 is associated with GR and JNK1. In peripheral blood mononuclear cells from severe asthmatics, DUSP4 expression was reduced versus healthy subjects and negatively correlated with phosphorylation levels of GR-Ser226 and JNK1. Formoterol enhanced DUSP4 activity and restored corticosteroid sensitivity reduced by DUSP4 siRNA. In conclusion, DUSP4 regulates corticosteroid sensitivity via dephosphorylation of JNK1 and GR-Ser226 DUSP4 activation by formoterol restores impaired corticosteroid sensitivity, indicating that DUSP4 is crucial in regulating corticosteroid sensitivity, and therefore might be a novel therapeutic target in severe asthma.


Depression in parents of children with cerebral palsy in Bosnia and Herzegovina.
The aim of the research is to examine depression in parents of children with cerebral palsy, with hypothesis to have more depressive symptom among mothers of children with cerebral palsy. The sample of examinees (between 23 and 62 age) was used in this research. The first subsample of examinees (N=23) was made of mothers (average 33±5.83) of children with cerebral palsy. The second subsample of examinees (N=12) was made of fathers of children with cerebral palsy (average 38±9.8). The third subsample of examinees (N=16) represented the control group, and it was made of mothers of children without disorders (average 38±6.57). For the purpose of quantitative measurement of depression, the Zung self-evaluated method for depression was applied. All data research were processed by parametric and nonparametric statistics. The frequencies and percents were also calculated, and Kruskal-Valis single-factor analysis of variants was applied for checking the hypothesis. According to the results of this research, it was concluded that there was no statistically significant difference in the evaluation of depression between mothers and fathers of children with cerebral palsy, as well as there is no statistically significant difference in relation to mothers of children without disorders.


[Drug-related disorders of water and electrolyte metabolism].
Pharmacologic treatment may lead to diverse disturbances of water and electrolyte metabolism as adverse drug events. Diuretics are particularly likely to cause these complications typically including volume depletion, metabolic alkalosis, hyponatremia, and hypokalemia. Salt and water retention with edema formation is most frequently elicited by antihypertensives, steroid hormones, and nonsteroidal anti-inflammatory drugs. Drug-induced disorders of Na+ concentration may usually be attributed to altered antidiuretic hormone (ADH) effects, either as diabetes insipidus or as the syndrome of inappropriate ADH secretion. With hyper- and hypokalemia, redistribution between intra- and extracellular fluid as well as renal excretion play a role. Strategies to prevent these adverse drug reactions include careful consideration of risk factors and clinical and laboratory controls in the course of treatment.


Defective expression of prohormone convertase 1/3 in silent corticotroph adenoma.
Silent corticotroph adenoma (SCA) is defined as an ACTH-producing pituitary tumor not associated with clinical and endocrine feartures of Cushing's syndrome, but its underlying molecular mechanism(s) remains unknown thus far. We tested the hypothesis that reduced expression of prohormone convertase (PC) 1/3 responsible for proteolytic processing of proopiomelanocortin (POMC) in SCA may lead to production of unprocessed, biologically inactive POMC and/or precursor of ACTH. Among 30 non-functioning pituitary macroadenomas (NFA) examined, we found 6 SCAs by immunohistochemical study using anti-ACTH antibody. Preoperative endocrine and diagnostic image tests did not reveal any differences between SCA and the remaining NFA except for the higher recurrence rate of SCA. While steady-state PC1/3 mRNA levels determined by RT-PCR were almost comparable between SCAs and NFAs, immunohistochemical study showed negative immunostaining for PC1/3 in all 6 SCAs. Our data suggest that defective PC1/3 expression may lead to preferential production of unprocessed, biologically inactive ACTH variants in SCA.


Effect of Acid-Suppressive Strategies on Pazopanib Efficacy in Patients With Soft-Tissue Sarcoma.
Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid-suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real-world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression-free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety-one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the PAZ only group. Median PFS was significantly shorter in the PAZ + ASM group than the PAZ only group (5.3 vs. 6.7 months). The PAZ + ASM group also had a 74% higher relative risk of progression or death than the PAZ only group, but there was no difference in OS. Regarding adverse events, the PAZ + ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that ASM should be avoided in patients with STS receiving PAZ. Larger studies are needed to further elucidate the impact of ASM use with PAZ in clinical practice.


Otitis media with effusion and chronic upper respiratory tract infection in children: a randomized, placebo-controlled clinical study.
This study was performed to investigate the course of spontaneous recovery from otitis media with effusion in children with chronic rhinosinusitis treated in various ways. One hundred forty-one children between 3 and 10 years of age were selected for the presence of chronic rhinosinusitis and unilateral or bilateral otitis media with effusion. The children were assigned at random to one of four treatment groups, i.e., placebo, amoxicillin combined with xylometazoline hydrochloride nose drops, maxillary sinus drainage, or a combination of the latter two forms of therapy. The follow-up period was 6 months. Drainage of the maxillary sinus had no effect on either the recovery of the chronic upper respiratory tract infection or otitis media with effusion. Amoxicillin combined with xylometazoline nose drops had no significant effect on recovery from the upper respiratory tract infection, but did have a small but significant effect on recovery from otitis media with effusion. However, the general tendency of the upper respiratory tract and ears to recover was poor. Persistence of the chronic upper respiratory tract infection during the follow-up period proved to be a negative prognostic factor with respect to cure of otitis media with effusion. Children with chronic rhinosinusitis as defined in this study appear to have a high risk of developing chronic otitis media with effusion. The results of the study are discussed.


[PCR-RFLP analysis of the Tams1 gene of Theileria annulata].
Tams1 is a merozoite surface antigen of Theileria annulata. Genetical variations of Tams1 make studies of vaccine and diagnostic tests like ELISA difficult. In this study, Tams1 genes of 89 T. annulata isolates obtained from natural infected cattle in Elazig and Bingöl regions were tested with PCR-RFLP. Six different restriction profiles (a, b, c, d, e, f) were detected. The number of restriction profiles of 89 samples was found to be as follows: 78(a), 2(b), 2(c), 5(d), 1(e), and 1(f).


Ambulatory Evaluation of ECG Signals Obtained Using Washable Textile-Based Electrodes Made with Chemically Modified PEDOT:PSS.
A development of washable PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate) polyamide textile-based electrodes is an interesting alternative to the traditional Ag/AgCl disposable electrodes, usually used in clinical practice, helping to improve medical assessment and treatment before apparition or progress of patients' cardiovascular symptoms. This study was conducted in order to determine whether physical properties of PEDOT:PSS had a significant impact on the coated electrode's electrocardiogram (ECG) signal quality, particularly after 50 washing cycles in a domestic laundry machine. Tests performed, included the comparison of two PEDOT:PSS solutions, in term of viscosity with emphasis on wetting tests, including surface tension and contact angle measurements. In addition, polyamide textile fabrics were used as substrate to make thirty electrodes and to characterize the amount of PEDOT:PSS absorbed as a function of time. The results showed that surface tension of PEDOT:PSS had a significant impact on the wetting of polyamide textile fabric and consequently on the absorbed amount. In fact, lower values of surface tension of the solution lead to low values contact angles between PEDOT:PSS and textile fabric (good wettability). Before washing, no significant difference has been observed among signal-to-noise ratios measured (SNR) for coated electrodes by the two PEDOT:PSS solutions. However, after 50 washing cycles, SNR decreased strongly for electrodes coated by the solution that had low viscosity, since it contained less solid contents. That was confirmed by scanning electron microscopy images (SEM) and also by analyzing the color change of electrodes based on the calculation of CIELAB color space coordinates. Moreover, spectral power density of recorded ECG signals has been computed and presented. All cardiac waves were still visible in the ECG signals after 50 washing cycles. Furthermore, an experienced cardiologist considered that all the ECG signals acquired were acceptable. Accordingly, our newly developed polyamide textile-based electrodes seem to be suitable for long-term monitoring. The study also provided new insights into the better choice of PEDOT:PSS formulation as a function of a specific process in order to manufacture cheaper electrodes faster.


[Total Hip arthroplasty in patients younger than 50 years].
Total hip replacement can provide pain relief and restore function in patients suffering from hip arthritis, including in those under the age of 50. However, shortened implant longevity in this age group has been a concern because the clinical results after revision surgery are inferior to those after primary hip arthroplasty. Technical choices (approach, implants, type of fixation and bearing couple) must be made to maximise longevity based on published data and thoroughly discussed with the patient. Finally, long term results (clinical outcome and implant longevity) associated with this surgery are such that it appears unnecessary to postpone the surgery once the indication is established.


Strategies for the design of orally bioavailable antileishmanial treatments.
Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. The most serious, life-threatening form is visceral leishmaniasis (VL). No vaccine is yet available for human use and chemotherapy is the main mean of dealing with this disease. This review focuses on the development of drug delivery systems (DDS) for treatment of leishmaniasis. After an overview of the significance of leishmaniasis in 2013, current chemotherapy and its limitations are considered, leading to possible strategies to improve the treatment of VL: new drugs, combinations of existing drugs and DDS, particularly for oral administration. Nanostructured biomaterials such as lipid-based or polymeric nanoparticles have unique physicochemical properties, ultra-small and controllable size, large surface area to mass ratio and the possibility of surface modification which can be used to advantage for the oral administration of antileishmanial drugs. They can improve the rate of dissolution of poorly water-soluble drugs, increase intestinal residence time by bioadhesion and, especially when lipid additives are used, influence the route and efficiency of absorption. These recent advances in this very active field should lead to better management of this serious disease.


Rapid additive-free selenocystine-selenoester peptide ligation.
We describe an unprecedented reaction between peptide selenoesters and peptide dimers bearing N-terminal selenocystine that proceeds in aqueous buffer to afford native amide bonds without the use of additives. The selenocystine-selenoester ligations are complete in minutes, even at sterically hindered junctions, and can be used in concert with one-pot deselenization chemistry. Various pathways for the transformation are proposed and probed through a combination of experimental and computational studies. Our new reaction manifold is also showcased in the total synthesis of two proteins.


[Ultrasonography and magnetic resonance imaging in diagnosing recurrent and metastatic ovarian cancer].
The paper deals with the capacities of ultrasonography (USG) and magnetic resonance imaging (MRI) in diagnosing recurrent and metastatic ovarian cancer along with routine clinical and laboratory studies (physical examination, measurement of the tumor-associated serum antigen CA-125) in 95 patients with ovarian cancer after primary special treatment. MRI is preferable to USG in evaluating the extent of a tumorous process and the invasion of a tumor into the adjacent tissues, which is of great value in defining a further treatment policy.


Herpesvirus hominis infection in newborn mice: treatment with interferon inducer polyinosinic-polycytidylic acid.
Intranasal inoculation of newborn mice with Herpesvirus hominis (HVH) type 2 provides a model for disseminated herpesvirus infections of human newborn infants. Treatment of this experimental infection with polyinosinic-polycytidylic acid [poly(I:C)] significantly increased the mean survival time and markedly altered the pathogenesis of the infection. No significant protection against final mortality was observed. Poly(I:C) therapy completely inhibited detectable viral replication in all target organs tested except the brain. In the brain there was a 2-day delay in the onset of viral replication in treated animals, which correlated with the 1- to 2-day increase in mean survival time. In general, the control of HVH replication occurred in those target organs in which poly(I:C)-induced interferon was detectable. The failure of poly(I:C) to alter the final mortality of newborn mice infected with HVH appears to be primarily due to the lack of sufficient levels of interferon induced in brain tissue and the failure to prevent viral replication in this critical target organ.


Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population. Spain, 1998-2014.
The mumps vaccine (Jeryl-Lynn-strain) was introduced in Spain in 1981, and a vaccination policy which included a second dose was added in 1995. From 1992-1999, a Rubini-strain based vaccine was administered in many regions but later withdrawn due to lack of effectiveness. Despite high levels of vaccination coverage, epidemics have continued to appear. We characterized the three epidemic waves of mumps between 1998 and 2014, identifying major changes in susceptible populations using Poisson regression. For the period 1998-2003 (P1), the most affected group was from 1 to 4years old (y) [Incidence Rate (IR)=71.7 cases/100,000 population]; in the periods 2004-2009 (P2) and 2010-2014 (P3) IR ratio (IRR) increased among 15-24y (P2=1.46; P3=2.68) and 25-34y (P2=2.17; P3=4.05). Hospitalization rate (HR), complication rate (CR) and neurological complication rate (NR) among hospitalized subjects decreased across the epidemics, except for 25-34y which increased: HR ratio (HRR) (P2=2.18; P3=2.16), CRR (P3=2.48), NRR (P3=2.41). In Spain mumps incidence increased, while an overall decrease of hospitalizations and severe complications occurred across the epidemics. Cohorts born during periods of low vaccination coverage and those vaccinated with Rubini-strain were the most affected populations, leading to a shift in mumps cases from children to adolescents and young adults; this also reveals the waning immunity provided by the mumps vaccine. Despite not preventing all mumps cases, the vaccine appears to prevent serious forms of the disease.


Should men treat women? Dilemmas for the male psychotherapist: psychoanalytic and developmental perspectives.
A spate of sexual abuse cases predominantly involving male psychotherapists with female patients as their victims raises serious questions about the ethics of cross-gender therapeutic dyads. Although such abusive situations must be highlighted as ethically aberrant, they may well represent a type of intrusive harm or hostile neglect which ensues on a continuum in the psychotherapeutic treatment of many female patients by male clinicians. I argue that the difficulties for men in empathically understanding women stem not only from certain misconceptions about women's development but especially stem from a paucity of understanding concerning men's psychology, a dearth of gender-sensitive information about the differences between boy's and girl's/men's and women's development, and a consequent difficulty for male psychotherapists to engage in the type of productive self-analysis that would ameliorate this gender-biased myopia. Recent psychoanalytically oriented child development/family research and innovative revisions of psychoanalytic theory are used to highlight some of the often overlooked, yet salient aspects of men's development as it is differentiated from women's. Specifically addressed is the possibility of a male, gender-linked vulnerability for a normative traumatic abrogation of the early holding environment with predictable sequelae in later intimate relationships, including the psychotherapeutic encounter. As the "confusion of tongues" between men's and women's development comes to light, is translated, and is empathically understood, new hope may be found for male therapists and their patients. An opportunity for enhanced therapeutic efficacy within an ethical and genuinely caring depth psychology may then be generated.


Sequence characterization and comparative analysis of the gastrotropin gene in buffalo (Bubalus bubalis).
In this study, we compared the complete sequence of the FABP6 gene from an animal representing the Murrah breed of the river buffalo (Bubalus bubalis) with the gene sequence from different mammals. The buffalo FABP6 gene is 6105 bp in length and is organized into four exons (67, 176, 90, and 54 bp), three introns (1167, 1737, and 2649 bp), a 5ꞌUTR (93 bp), and a 3ꞌUTR (72 bp). A total of 22 repetitive elements were identified at the intronic level, and four of these (L1MC, L1M5, MIRb, and Charlie4z) were identified as being exclusive to buffalo. Comparative analysis between the FABP6 gene coding sequence and the amino acid sequence with its homologues from other mammalian species showed a percentage of identity varying from 79 to 98% at the DNA coding level and 70 to 96% at the amino acid level. In addition, the alignment of the gene sequence between the Murrah and the Mediterranean breeds revealed 20 potential single nucleotide polymorphisms, which could be candidates for validation in commercial buffalo populations.


Compound nanostructure capable of realizing full-spectrum utilization of solar energy for PV-TE hybrid systems.
The photovoltaic-thermoelectric (PV-TE) hybrid system can achieve full-spectrum utilization of the solar spectrum, but surface reflection has always been an important reason to suppress its power conversion efficiency. Therefore, a novel composite nanostructure (CN) is proposed by the finite-difference time-domain (FDTD) simulation method to reduce the surface reflection in the spectral range of 0.3-2.5 μm, which consists of a pyramid and grating structure. For the sake of generality, this paper studies the spectral reflectance of the CN under multiple parameters. The results show that the CN integrated pyramid and grating correspond to excellent anti-reflection performance in the short wavelength range and long wavelength range, respectively, compared to a unitary structure, achieving anti-reflection in the full spectral range. In addition, the CN expresses the insensitivity to the structural parameters, and has lower reflectivity compared with a commercial battery. The mechanism for achieving this full-spectrum anti-reflection is mainly to enhance the path of light in the medium to enhance absorption and achieve high transmission under the action of the waveguide. This paper implements ultra-broadband anti-reflection of a compound nanostructure for full-spectrum utilization of solar energy, and provides a solution to improve the power conversion efficiency of PV-TE hybrid systems.


The histopathology of small arteries following experimental microvascular anastomosis.
We studied the histopathological changes present at various intervals after microsurgical anastomoses in the femoral arteries of 30 rats. The principal findings were (1) widespread loss of intima, (2) widespread necrosis of media, and (3) dehiscence of sutures. The possible causes for these, and their possible significance, are discussed.


The Mediating Effect of Self-Efficacy on the Relationship Between Medication Literacy and Medication Adherence Among Patients with Type 2 Diabetes.
Patients with type 2 diabetes have poor medication adherence. Medication literacy is one of the influencing factors of medication adherence among patients with type 2 diabetes. However, the mechanism by which medication literacy affects medication adherence among patients with type 2 diabetes is unclear. The aim of this study was to verify the mediating role of self-efficacy in the relationship between medication literacy and medication adherence. A total of 402 patients with type 2 diabetes were enrolled in this study. The Chinese versions of the Medication Literacy Scale, the Self-Efficacy for Appropriate Medication Use Scale and the Morisky Medication Adherence Scale-8 were used in the survey. Pearson correlation analysis was used to find correlations among medication literacy, self-efficacy and medication adherence. The PROCESS macro (Version 4.1) with Model 4 for SPSS was used to verify the mediating role of self-efficacy. Twenty-four percent of the participants had poor medication adherence. Self-efficacy and medication literacy (r=0.499, p < 0.01) and medication adherence (r=0.499, p < 0.01) were significantly and positively correlated. Self-efficacy partially mediated the relationship between medication knowledge and medication adherence among patients with type 2 diabetes, accounting for 36.7% of the total effect. Self-efficacy had a partial mediating effect on the relationship between medication literacy and medication adherence among patients with type 2 diabetes. Self-efficacy should be improved through effective measures to increase patients' confidence in adherence to antihyperglycemic drugs.


Chromatin structure is distinct between coding and non-coding single nucleotide polymorphisms.
Previous studies suggested that nucleosomes are enriched with single nucleotide polymorphisms (SNPs) in humans and that the occurrence of mutations is closely associated with CpG dinucleotides. We aimed to determine if the chromatin organization is genomic locus specific around SNPs, and if newly occurring mutations are associated with SNPs. Here, we classified SNPs according their loci and investigated chromatin organization in both CD4+ T cell and lymphoblastoid cell in humans. We calculated the SNP frequency around somatic mutations. The results indicated that nucleosome occupancy is different around SNPs sites in different genomic loci. Coding SNPs are mainly enriched at nucleosomes and associated with repressed histone modifications (HMs) and DNA methylation. Contrastingly, intron SNPs occur in nucleosome-depleted regions and lack HMs. Interestingly, risk-associated non-coding SNPs are also enriched at nucleosomes with HMs but associated with low GC-content and low DNA methylation level. The base-transversion allele frequency is significantly low in coding-synonymous SNPs (P < 10⁻¹¹). Another finding is that at the -1 and +1 positions relative to the somatic mutation sites, the SNP frequency was significantly higher (P < 3.2 × 10⁻⁵). The results suggested chromatin structure is different around coding SNPs and non-coding SNPs. New mutations tend to occur at the -1 and +1 position immediately near the SNPs.


Evaluation of parameters of a plankton community's biological rhythms under the natural environment of the Black Sea using the Fourier transform method.
Night-time changes in bioluminescence intensity in the coastal area of the Black Sea were recorded. It was noted that the biomass of luminous organisms is closely correlated with the biomass of plankton and other pelagic organisms, including commercial pelagic fish. The parameters of plankton communities' basic biological rhythms were determined using the discrete Fourier transform method. These rhythms were manifest as spatial and temporal changes in the bioluminescence intensity. It was shown that changes in the bioluminescence intensity over a 14.0-h period were due to the duration of the light/dark cycles. By contrast, changes in bioluminescence intensity with periods of 4.7 and 2.8 h were due to the endogenous rhythms of the plankton community (feeding and cell division). An original method for evaluating of errors in the calculated periods of the biological rhythms was proposed. A strong correlation (r = 0.906) was observed between the measured and calculated values for the bioluminescence intensity, which provided support for the assumptions made.


Glucose metabolism of Treponema bryantii, an anaerobic rumen spirochete.
The pathway of glucose metabolism by Treponema bryantii, an obligately anaerobic spirochete isolated from bovine rumen contents, was studied. Washed cell suspensions of the spirochete consumed glucose and CO2 and produced equimolar amounts of acetate, formate, and succinate. Carbon dioxide was essential for glucose metabolism. Determination of radioactivity in products formed from 14C-labelled glucose and NaH14CO3 and assays of enzyme activities in cell-free extracts were used to determine the pathway of glucose metabolism. Treponema bryantii catabolized glucose to pyruvate via the Embden--Meyerhof--Parnas pathway. The spirochete used a coliform pyruvate-formate lyase to degrade pyruvate and produce formate and acetate. Succinate was formed by a pathway which involved the condensation of CO2 with pyruvate (or phospho(enol)pyruvate) formed from the breakdown of glucose.